The present invention is generally in the area of targeting delivery of nucleotides and other molecules to large vessel endothelium using the endothelial cell protein C/activated protein C receptor (“EPCR”).
Endothelial cells are a primary defense mechanism against cellular infiltration and thrombosis. Abnormal function of the endothelial cells contributes to myocardial infarction (MI), stroke and the development of atherosclerotic plaque. Atherosclerosis and most other vascular disease primarily occur in large vessels. In particular, large vessels are prone to a variety of diseases leading to atherosclerosis and thrombosis, resulting in heart attacks, strokes, deep vein thrombosis and pulmonary emboli. Gene therapy to modify the vascular lesions would be desirable.
Unfortunately, targeting endothelial cells non-specifically is often inadequate. Since more than 95% of endothelial cells are in the capillaries, arterioles and postcapillary venules, any therapy directed toward endothelial cells per se runs the risk of systemic complications. One must be confident that the gene expression is limited to the desired cells when using a gene therapy approach. However, no means for specifically targeting delivery to large vessel endothelium, in contrast to small vessel endothelium, or other types of tissues, are known.
It is therefore an object of the present invention to provide a means for specifically targeting delivery to large vessel endothelium.
It is a further object of the present invention to provide a means for delivering an agent to the endothelial cell nucleus of large vessels.